Elliptocytosis

Elliptical, anucleate erythrocytes from a llama. A lymphocyte also is present. Llama, blood smear, Wright-Leishman stain.

Elliptical, nucleated erythrocytes are a normal hematological finding in certain vertebrates such as birds. A monocyte also is present. Amazon parrot, blood smear, Wright-Leishman stain.

Elliptocytes or ovalocytes (arrow) in the blood smear of a cat following doxorubicin treatment. A macroplatelet is present in the upper lefthand corner. Cat, blood smear, Wright-Leishman stain.

Elliptocytes (ovalocytes) are non-nucleated erythrocytes that are ovoid to elliptical in shape and are usually flat instead of the standard biconcave shape. This oval shape is a normal finding for animals in the Camelidae family (camels, llamas, alpacas, etc.) Circulating, mature erythrocytes of birds, reptiles, amphibians, and fish also are elliptical; however, the nucleus is normally retained. Elliptocytes can be present in the blood of healthy animals, but usually comprise <1% of erythrocyte population. Larger numbers of elliptocytes in the stained blood film usually indicate the presence of acquired or congenital disease.

Acquired diseases (see below) usually result in <10% elliptocytes; however, up to 50% of the erythrocytes may be elliptocytes in dyserythropoises. In hereditary elliptocytosis the percentage of elliptocytes may vary from 0% to 98%.4 Elliptocytosis was first described in blood smears from humans in 1904 and was later demonstrated to be hereditary.4 The first reported case of hereditary elliptocytosis (HE) was described by Smith in 1983.5 Since the original description in human beings, HE has also been reported in mice.

Elliptocytosis is the term generally used to describe conditions in which the erythrocytes are ovoid to elliptical in shape. Ovalocytosis is a term usually reserved for a rarer condition in which erythrocytes appear more oval and lack a central concavity. Spherocytes also may be present in the blood film. In humans, this condition has been designated Southeast Asian ovalocytosis, Melanesian ovalocytosis, or stomatocytic HE. Affected erythrocytes typically are more round than elliptical and have a longitudinal or transverse slit.

Contents

Erythrocyte Structure

The erythrocyte is a relatively simple cell, composed of only a membrane and cytoplasm. Energy is provided via glycolysis and mature mammalian erythrocytes are anucleate. Membrane structure is important in the formation of elliptocytes and ovalocytes. The cell membrane is composed of lipid and the cytoskeleton (Fig. 4). The "lipid portion" of the membrane actually consists of cholesterol, phospholipids, and protein. The cytoskeleton is formed by several proteins (spectrin, ankyrin, actin, and protein 4.1) that are arranged beneath and interact with the lipid layer. This cytoskeleton is vital to the integrity and stability of the erythrocyte. Deficiencies of any of the proteins may result in an altered erythrocyte cytoskeletal structure. This change is reflected by an inability of the erythrocyte to alter shape when passing through capillary beds.8 In HE, the membrane change is due to an abnormality of the cytoskeletal protein spectrin (protein 4.1). This results in decreased deformability of affected erythrocytes as they traverse the capillary beds of the body.

Schematic diagram of the erythrocyte cell membrane (courtesy of Dr. Guillaume Lenormand, Harvard School of Public Health, Boston, MA, 02115-6021).

Causes

Clinical Signs

The clinical signs of elliptocytosis are highly variable, depending on the cause of the red blood cell defect and the species affected. Human carriers of HE may lack signs of disease. In individuals affected with HE, the degree of anemia may be variable. People with mild HE may have a mild but fully compensated anemia. Patients with HE of moderate severity may present with a moderate, incompletely compensated hemolytic anemia with splenomegaly. Patients with incompletely compensated anemia also are susceptible to more severe, acute, anemic crises that can be triggered by stress and other disease processes. In severe cases of chronic hemolytic anemia, treatment may include blood transfusions and splenectomy. There also are variants of HE where the disease is severe in newborns and gradually decreases in severity with age. A specific variant of HE, Southeast Asian ovalocytosis, is seen in humans in southeast Asia where the red blood cell is more rigid than normal and resists invasion by malaria parasites.

The clinical signs of hereditary elliptocytosis in the dog are minimal to nil, and the disease usually is diagnosed incidentally. Theoretically, dogs with HE could present with episodes of severe hemolytic anemia, but this has not been documented yet.

Diagnosis

Elliptocytosis and ovalocytosis are diagnosed by microscopic examination of the stained blood smear. These abnormally shaped erythrocytes generally are not detected by automated hematology analyzers. As a result, diagnosis of elliptocytosis in people and animals is incidental.

Treatment

In humans, severe cases of HE are often treated by splenectomy. Blood transfusions may be necessary in cases of noncompensated hemolytic anemia.4,18 Treatment of elliptocytosis in dogs is not well documented. Elliptocytosis usually is an incidental finding on blood smear examination. Clinical signs of disease are rare and usually do not require treatment.

Summary

Elliptocytes are erythrocytes that are oval to elliptical in shape. They are a normal finding in birds, reptiles, amphibians, fish, and members of the Camelidae family (camels, llamas, alpacas). In other mammals, elliptocytosis (ovalocytosis) is an uncommon morphologic change of erythrocytes due to inherited or acquired disease. HE has been documented in humans, dogs, and mice as a result of erythrocyte membrane protein mutation or deficiency. In humans, Southeastern Asian ovalocytosis is a specific form of HE in which the erythrocyte are more malaria-resistant. Acquired elliptocytosis is not as well documented, but often is associated with hemolytic anemia in humans. In dogs and cats, elliptocytosis usually is an incidental finding related to systemic disease. Treatment of HE in humans is variable depending on the severity of the disease and associated hemolytic anemia. Blood transfusions and splenectomy sometimes are required in severe hemolytic anemia. In contrast, treatment in animals is poorly documented. Because most cases of elliptocytosis to date are diagnosed as incidental findings, this condition is not necessarily treated per se. However, therapy may be recommended for the underlying cause of the disease.